Butyrate alleviates renal fibrosis in CKD by regulating NLRP3-mediated pyroptosis via the STING/NF-κB/p65 pathway
•Butyrate levels exhibited a decreasing trend with the progression of CKD.•Butyrate alleviated renal fibrosis in CKD mice.•Butyrate suppressed NLRP3-mediated pyroptosis.•Butyrate inhibited NLRP3-mediated pyroptosis via the STING/NF-κB/p65 pathway. Chronic kidney disease (CKD) is a serious and irreve...
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Veröffentlicht in: | International immunopharmacology 2023-11, Vol.124, p.111010-111010, Article 111010 |
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container_title | International immunopharmacology |
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creator | Tian, Xiaofang Zeng, Yizhou Tu, Qingxian Jiao, Yang Yao, Song Chen, Ying Sun, Li Xia, Qianhang Luo, Yadan Yuan, Liying Jiang, Qianfeng |
description | •Butyrate levels exhibited a decreasing trend with the progression of CKD.•Butyrate alleviated renal fibrosis in CKD mice.•Butyrate suppressed NLRP3-mediated pyroptosis.•Butyrate inhibited NLRP3-mediated pyroptosis via the STING/NF-κB/p65 pathway.
Chronic kidney disease (CKD) is a serious and irreversible disease primarily characterized by chronic inflammation and renal fibrosis. Recent studies have suggested that gut microbiota-related metabolites, particularly short-chain fatty acids (SCFAs) are significantly associated with kidney diseases. Notably, butyrate, a type of SCFAs, plays a crucial role in this correlation. However, the effect of butyrate on renal fibrosis in patients with CKD and its potential mechanisms remain unclear. In this study, we demonstrated that butyrate levels are reduced as CKD progresses using a CKD C57BL/6 mouse model established by a 0.2% adenine diet. Exogenous supplementation of butyrate effectively alleviated renal fibrosis and repressed the levels of proteins associated with NLRP3-mediated pyroptosis (NLRP3, IL-1β, caspase-1, and GSDMD). Additionally, we conducted an in vitro experiment using HK-2 cells, which also confirmed that the elevated levels of NLRP3-mediated pyroptosis proteins in TGF-β1-stimulated HK-2 cells are reversed by butyrate intervention. Further, butyrate mitigated the activity of the STING/NF-κB/p65 pathway, and STING overexpression impaired the protective function of butyrate in CKD. Hence, we suggest that butyrate may have a renoprotective role in CKD, alleviating renal fibrosis possibly by regulating NLRP3-mediated pyroptosis via the STING/NF-κB/p65 pathway. |
doi_str_mv | 10.1016/j.intimp.2023.111010 |
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Chronic kidney disease (CKD) is a serious and irreversible disease primarily characterized by chronic inflammation and renal fibrosis. Recent studies have suggested that gut microbiota-related metabolites, particularly short-chain fatty acids (SCFAs) are significantly associated with kidney diseases. Notably, butyrate, a type of SCFAs, plays a crucial role in this correlation. However, the effect of butyrate on renal fibrosis in patients with CKD and its potential mechanisms remain unclear. In this study, we demonstrated that butyrate levels are reduced as CKD progresses using a CKD C57BL/6 mouse model established by a 0.2% adenine diet. Exogenous supplementation of butyrate effectively alleviated renal fibrosis and repressed the levels of proteins associated with NLRP3-mediated pyroptosis (NLRP3, IL-1β, caspase-1, and GSDMD). Additionally, we conducted an in vitro experiment using HK-2 cells, which also confirmed that the elevated levels of NLRP3-mediated pyroptosis proteins in TGF-β1-stimulated HK-2 cells are reversed by butyrate intervention. Further, butyrate mitigated the activity of the STING/NF-κB/p65 pathway, and STING overexpression impaired the protective function of butyrate in CKD. Hence, we suggest that butyrate may have a renoprotective role in CKD, alleviating renal fibrosis possibly by regulating NLRP3-mediated pyroptosis via the STING/NF-κB/p65 pathway.</description><identifier>ISSN: 1567-5769</identifier><identifier>EISSN: 1878-1705</identifier><identifier>DOI: 10.1016/j.intimp.2023.111010</identifier><language>eng</language><publisher>Elsevier B.V</publisher><subject>NF-κB/p65 ; NLRP3 inflammasome ; Pyroptosis ; Renal fibrosis ; Short-chain fatty acids</subject><ispartof>International immunopharmacology, 2023-11, Vol.124, p.111010-111010, Article 111010</ispartof><rights>2023 Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c339t-e6b348089010cc066d2b39c8c27d3472ea4e59cf7c162c4a9c3c3e280172251c3</citedby><cites>FETCH-LOGICAL-c339t-e6b348089010cc066d2b39c8c27d3472ea4e59cf7c162c4a9c3c3e280172251c3</cites><orcidid>0009-0004-6070-7013</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.intimp.2023.111010$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids></links><search><creatorcontrib>Tian, Xiaofang</creatorcontrib><creatorcontrib>Zeng, Yizhou</creatorcontrib><creatorcontrib>Tu, Qingxian</creatorcontrib><creatorcontrib>Jiao, Yang</creatorcontrib><creatorcontrib>Yao, Song</creatorcontrib><creatorcontrib>Chen, Ying</creatorcontrib><creatorcontrib>Sun, Li</creatorcontrib><creatorcontrib>Xia, Qianhang</creatorcontrib><creatorcontrib>Luo, Yadan</creatorcontrib><creatorcontrib>Yuan, Liying</creatorcontrib><creatorcontrib>Jiang, Qianfeng</creatorcontrib><title>Butyrate alleviates renal fibrosis in CKD by regulating NLRP3-mediated pyroptosis via the STING/NF-κB/p65 pathway</title><title>International immunopharmacology</title><description>•Butyrate levels exhibited a decreasing trend with the progression of CKD.•Butyrate alleviated renal fibrosis in CKD mice.•Butyrate suppressed NLRP3-mediated pyroptosis.•Butyrate inhibited NLRP3-mediated pyroptosis via the STING/NF-κB/p65 pathway.
Chronic kidney disease (CKD) is a serious and irreversible disease primarily characterized by chronic inflammation and renal fibrosis. Recent studies have suggested that gut microbiota-related metabolites, particularly short-chain fatty acids (SCFAs) are significantly associated with kidney diseases. Notably, butyrate, a type of SCFAs, plays a crucial role in this correlation. However, the effect of butyrate on renal fibrosis in patients with CKD and its potential mechanisms remain unclear. In this study, we demonstrated that butyrate levels are reduced as CKD progresses using a CKD C57BL/6 mouse model established by a 0.2% adenine diet. Exogenous supplementation of butyrate effectively alleviated renal fibrosis and repressed the levels of proteins associated with NLRP3-mediated pyroptosis (NLRP3, IL-1β, caspase-1, and GSDMD). Additionally, we conducted an in vitro experiment using HK-2 cells, which also confirmed that the elevated levels of NLRP3-mediated pyroptosis proteins in TGF-β1-stimulated HK-2 cells are reversed by butyrate intervention. Further, butyrate mitigated the activity of the STING/NF-κB/p65 pathway, and STING overexpression impaired the protective function of butyrate in CKD. Hence, we suggest that butyrate may have a renoprotective role in CKD, alleviating renal fibrosis possibly by regulating NLRP3-mediated pyroptosis via the STING/NF-κB/p65 pathway.</description><subject>NF-κB/p65</subject><subject>NLRP3 inflammasome</subject><subject>Pyroptosis</subject><subject>Renal fibrosis</subject><subject>Short-chain fatty acids</subject><issn>1567-5769</issn><issn>1878-1705</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kE1OwzAQhSMEEqVwAxZesknrnyRONki00FJRFQRlbbnOtHWVJsF2inI1DsGZcAlrVjOaee9J7wuCa4IHBJNkuBvo0ul9PaCYsgEh_ohPgh5JeRoSjuNTv8cJD2OeZOfBhbU7jP09Ir3AjBrXGukAyaKAg_abRQZKWaC1XpnKaot0icZP92jV-semKaTT5QYt5q8vLNxDfrTkqG5NVbtfuQ9BbgvobTlbTIeLSfj9NRrWSYxq6bafsr0MztaysHD1N_vB--RhOX4M58_T2fhuHirGMhdCsmJRitPMl1EKJ0lOVyxTqaI8ZxGnICOIM7XmiiRURTJTTDGgqW9GaUwU6wc3XW5tqo8GrBN7bRUUhSyhaqygKc8izBnhXhp1UuUbWwNrURu9l6YVBIsjYrETHWJxRCw6xN5229nA1zhoMMIqDaXyUAwoJ_JK_x_wA_EhhmE</recordid><startdate>202311</startdate><enddate>202311</enddate><creator>Tian, Xiaofang</creator><creator>Zeng, Yizhou</creator><creator>Tu, Qingxian</creator><creator>Jiao, Yang</creator><creator>Yao, Song</creator><creator>Chen, Ying</creator><creator>Sun, Li</creator><creator>Xia, Qianhang</creator><creator>Luo, Yadan</creator><creator>Yuan, Liying</creator><creator>Jiang, Qianfeng</creator><general>Elsevier B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0009-0004-6070-7013</orcidid></search><sort><creationdate>202311</creationdate><title>Butyrate alleviates renal fibrosis in CKD by regulating NLRP3-mediated pyroptosis via the STING/NF-κB/p65 pathway</title><author>Tian, Xiaofang ; Zeng, Yizhou ; Tu, Qingxian ; Jiao, Yang ; Yao, Song ; Chen, Ying ; Sun, Li ; Xia, Qianhang ; Luo, Yadan ; Yuan, Liying ; Jiang, Qianfeng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c339t-e6b348089010cc066d2b39c8c27d3472ea4e59cf7c162c4a9c3c3e280172251c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>NF-κB/p65</topic><topic>NLRP3 inflammasome</topic><topic>Pyroptosis</topic><topic>Renal fibrosis</topic><topic>Short-chain fatty acids</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tian, Xiaofang</creatorcontrib><creatorcontrib>Zeng, Yizhou</creatorcontrib><creatorcontrib>Tu, Qingxian</creatorcontrib><creatorcontrib>Jiao, Yang</creatorcontrib><creatorcontrib>Yao, Song</creatorcontrib><creatorcontrib>Chen, Ying</creatorcontrib><creatorcontrib>Sun, Li</creatorcontrib><creatorcontrib>Xia, Qianhang</creatorcontrib><creatorcontrib>Luo, Yadan</creatorcontrib><creatorcontrib>Yuan, Liying</creatorcontrib><creatorcontrib>Jiang, Qianfeng</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International immunopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tian, Xiaofang</au><au>Zeng, Yizhou</au><au>Tu, Qingxian</au><au>Jiao, Yang</au><au>Yao, Song</au><au>Chen, Ying</au><au>Sun, Li</au><au>Xia, Qianhang</au><au>Luo, Yadan</au><au>Yuan, Liying</au><au>Jiang, Qianfeng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Butyrate alleviates renal fibrosis in CKD by regulating NLRP3-mediated pyroptosis via the STING/NF-κB/p65 pathway</atitle><jtitle>International immunopharmacology</jtitle><date>2023-11</date><risdate>2023</risdate><volume>124</volume><spage>111010</spage><epage>111010</epage><pages>111010-111010</pages><artnum>111010</artnum><issn>1567-5769</issn><eissn>1878-1705</eissn><abstract>•Butyrate levels exhibited a decreasing trend with the progression of CKD.•Butyrate alleviated renal fibrosis in CKD mice.•Butyrate suppressed NLRP3-mediated pyroptosis.•Butyrate inhibited NLRP3-mediated pyroptosis via the STING/NF-κB/p65 pathway.
Chronic kidney disease (CKD) is a serious and irreversible disease primarily characterized by chronic inflammation and renal fibrosis. Recent studies have suggested that gut microbiota-related metabolites, particularly short-chain fatty acids (SCFAs) are significantly associated with kidney diseases. Notably, butyrate, a type of SCFAs, plays a crucial role in this correlation. However, the effect of butyrate on renal fibrosis in patients with CKD and its potential mechanisms remain unclear. In this study, we demonstrated that butyrate levels are reduced as CKD progresses using a CKD C57BL/6 mouse model established by a 0.2% adenine diet. Exogenous supplementation of butyrate effectively alleviated renal fibrosis and repressed the levels of proteins associated with NLRP3-mediated pyroptosis (NLRP3, IL-1β, caspase-1, and GSDMD). Additionally, we conducted an in vitro experiment using HK-2 cells, which also confirmed that the elevated levels of NLRP3-mediated pyroptosis proteins in TGF-β1-stimulated HK-2 cells are reversed by butyrate intervention. Further, butyrate mitigated the activity of the STING/NF-κB/p65 pathway, and STING overexpression impaired the protective function of butyrate in CKD. Hence, we suggest that butyrate may have a renoprotective role in CKD, alleviating renal fibrosis possibly by regulating NLRP3-mediated pyroptosis via the STING/NF-κB/p65 pathway.</abstract><pub>Elsevier B.V</pub><doi>10.1016/j.intimp.2023.111010</doi><tpages>1</tpages><orcidid>https://orcid.org/0009-0004-6070-7013</orcidid></addata></record> |
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subjects | NF-κB/p65 NLRP3 inflammasome Pyroptosis Renal fibrosis Short-chain fatty acids |
title | Butyrate alleviates renal fibrosis in CKD by regulating NLRP3-mediated pyroptosis via the STING/NF-κB/p65 pathway |
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